tbuckley/cabot-search huggingface dataset:
Residential Exposure to Urban Trees and Medication Sales for Mood Disorders and Cardiovascular Disease in Brussels, Belgium: An Ecological Study
Authors: Dengkai Chi, Raf Aerts, An Van Nieuwenhuyse, Mariska Bauwelinck, Claire Demoury, Michelle Plusquin, Tim S. Nawrot, Lidia Casas, Ben Somers
Journal: Environmental Health Perspectives (2022)

The available evidence for positive associations between urban trees and human health is mixed, partly because the assessment of exposure to trees is often imprecise because of, for instance, exclusion of trees in private areas and the lack of three-dimensional (3D) exposure indicators (e.g., crown volume).We aimed to quantify all trees and relevant 3D structural traits in Brussels (Belgium) and to investigate associations between the number of trees, tree traits, and sales of medication commonly prescribed for mood disorders and cardiovascular disease.We developed a workflow to automatically isolate all individual trees from airborne light detection and ranging (LiDAR) data collected in 2012. Trait data were subsequently extracted for 309,757 trees in 604 census tracts. We used the average annual age-standardized rate of medication sales in Brussels for the period 2006 to 2014, calculated from reimbursement information on medication prescribed to adults (19-64 years of age). The medication sales data were provided by sex at the census tract level. Generalized log-linear models were used to investigate associations between the number of trees, the crown volume, tree structural variation, and medication sales. Models were run separately for mood disorder and cardiovascular medication and for men and women. All models were adjusted for indicators of area-level socioeconomic status.Single-factor models showed that higher stem densities and higher crown volumes are both associated with lower medication sales, but opposing associations emerged in multifactor models. Higher crown volume [an increase by one interquartile range (IQR) of 1.4×104 m³/ha] was associated with 34% lower mood disorder medication sales [women, β=-0.341 (95% CI: -0.379, -0.303); men, β=-0.340 (95% CI: -0.378, -0.303)] and with 21-25% lower cardiovascular medication sales [women, β=-0.214 (95% CI: -0.246, -0.182); men, β=-0.252 (95% CI: -0.285, -0.219)]. Conversely, a higher stem density (an increase by one IQR of 21.8 trees/ha) was associated with 28-32% higher mood disorder medication sales [women, β=0.322 (95% CI: 0.284, 0.361); men, β=0.281 (95% CI: 0.243, 0.319)] and with 20-24% higher cardiovascular medication sales [women, β=0.202 (95% CI: 0.169, 0.236); men, β=0.240 (95% CI: 0.206, 0.273)].We found a trade-off between the number of trees and the crown volumes of those trees for human health benefits in an urban environment. Our results demonstrate that conserving large trees in urban environments may not only support conservation of biodiversity but also human health. https://doi.org/10.1289/EHP9924.
A CRISPR view of hematopoietic stem cells: Moving innovative bioengineering into the clinic
Authors: Atesh K. Worthington, E. Camilla Forsberg
Journal: American Journal of Hematology (2022)

Clustered regularly interspaced short palindromic repeats (CRISPR)/Cas genome engineering has emerged as a powerful tool to modify precise genomic sequences with unparalleled accuracy and efficiency. Major advances in CRISPR technologies over the last 5 years have fueled the development of novel techniques in hematopoiesis research to interrogate the complexities of hematopoietic stem cell (HSC) biology. In particular, high throughput CRISPR based screens using various "flavors" of Cas coupled with sequencing and/or functional outputs are becoming increasingly efficient and accessible. In this review, we discuss recent achievements in CRISPR-mediated genomic engineering and how these new tools have advanced the understanding of HSC heterogeneity and function throughout life. Additionally, we highlight how these techniques can be used to answer previously inaccessible questions and the challenges to implement them. Finally, we focus on their translational potential to both model and treat hematological diseases in the clinic.
DCs at the center of help: Origins and evolution of the three-cell-type hypothesis
Authors: Renee Wu, Kenneth M. Murphy
Journal: The Journal of Experimental Medicine (2022)

Last year was the 10th anniversary of Ralph Steinman's Nobel Prize awarded for his discovery of dendritic cells (DCs), while next year brings the 50th anniversary of that discovery. Current models of anti-viral and anti-tumor immunity rest solidly on Steinman's discovery of DCs, but also rely on two seemingly unrelated phenomena, also reported in the mid-1970s: the discoveries of "help" for cytolytic T cell responses by Cantor and Boyse in 1974 and "cross-priming" by Bevan in 1976. Decades of subsequent work, controversy, and conceptual changes have gradually merged these three discoveries into current models of cell-mediated immunity against viruses and tumors.
Abstract A022: Effects of chemotherapy on the peripheral immune-cellome in patients with pancreatic cancer
Authors: Maja Svensson, Alexandra Petersson, Viktor Sincic, Sofie Olsson Hau, Jakob Eberhard, David Gisselsson Nord, Karin Leandersson, Kristina Lundberg, Karin Jirström
Journal: Cancer Research (2022)

Abstract Pancreatic cancer (PC) has become one of the leading causes of cancer related deaths. Late detection and resistance to therapy are two reasons for the dismal prognosis of this disease. Hence, there is an immense need for novel treatment options as well as predictive biomarkers, to prolong the life of these patients. The Chemotherapy, Host Response and Molecular Dynamics in Periampullary Cancer, the CHAMP study (clinical trial nr NCT03724994), is an ongoing observational, prospective clinical study that includes newly diagnosed patients with PC or other periampullary cancers receiving adjuvant or first-line palliative chemotherapy. The present study aims to investigate the peripheral immune-cellome in serial blood samples obtained during treatment from 24 patients, of whom 8 had resectable tumors. Buffy coat was isolated from blood samples taken at baseline (before treatment), after one month and after three to four months of treatment. Flow cytometry with two panels of antibodies was applied to detect major immune populations in both the innate and the adaptive immune system, as well as subpopulations of T cells. Immune cell frequencies were compared between patients with progression and no progression during treatment, and the associations of different immune cell subsets with overall survival were examined. As B cells have been highlighted as being of particular clinical relevance, single-cell transcriptomics and proteomics will be applied to further delineate the dynamics and prognostic impact of individual subtypes within this lineage. The results will provide important real-world data on the longitudinal dynamics of circulating immune cells under the pressure of chemotherapy in patients with PC. These results will in the future be related to analyses of circulating tumor DNA in matched blood samples, and together they will provide a foundation for forthcoming adaptive treatment trials based on results from the CHAMP study. Citation Format: Maja Svensson, Alexandra Petersson, Viktor Sincic, Sofie Olsson Hau, Jakob Eberhard, David Gisselsson Nord, Karin Leandersson, Kristina Lundberg, Karin Jirström. Effects of chemotherapy on the peripheral immune-cellome in patients with pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference on the Evolutionary Dynamics in Carcinogenesis and Response to Therapy; 2022 Mar 14-17. Philadelphia (PA): AACR; Cancer Res 2022;82(10 Suppl):Abstract nr A022.
Clinical features of, and risk factors for, severe or fatal COVID-19 among people living with HIV admitted to hospital: analysis of data from the WHO Global Clinical Platform of COVID-19
Authors: Silvia Bertagnolio, Soe Soe Thwin, Ronaldo Silva, Sairaman Nagarajan, Waasila Jassat, Robert Fowler, Rashan Haniffa, Ludovic Reveiz, Nathan Ford, Meg Doherty, Janet Diaz
Journal: The Lancet HIV (2022)

WHO has established a Global Clinical Platform for the clinical characterisation of COVID-19 among hospitalised individuals. We assessed whether people living with HIV hospitalised with COVID-19 had increased odds of severe presentation and of in-hospital mortality compared with individuals who were HIV-negative and associated risk factors.Between Jan 1, 2020, and July 1, 2021, anonymised individual-level data from 338 566 patients in 38 countries were reported to WHO. Using the Platform pooled dataset, we performed descriptive statistics and regression analyses to compare outcomes in the two populations and identify risk factors.Of 197 479 patients reporting HIV status, 16 955 (8·6%) were people living with HIV. 16 283 (96.0%) of the 16 955 people living with HIV were from Africa; 10 603 (62·9%) were female and 6271 (37·1%) were male; the mean age was 45·5 years (SD 13·7); 6339 (38·3%) were admitted to hospital with severe illness; and 3913 (24·3%) died in hospital. Of the 10 166 people living with HIV with known antiretroviral therapy (ART) status, 9302 (91·5%) were on ART. Compared with individuals without HIV, people living with HIV had 15% increased odds of severe presentation with COVID-19 (aOR 1·15, 95% CI 1·10-1·20) and were 38% more likely to die in hospital (aHR 1·38, 1·34-1·41). Among people living with HIV, male sex, age 45-75 years, and having chronic cardiac disease or hypertension increased the odds of severe COVID-19; male sex, age older than 18 years, having diabetes, hypertension, malignancy, tuberculosis, or chronic kidney disease increased the risk of in-hospital mortality. The use of ART or viral load suppression were associated with a reduced risk of poor outcomes; however, HIV infection remained a risk factor for severity and mortality regardless of ART and viral load suppression status.In this sample of hospitalised people contributing data to the WHO Global Clinical Platform for COVID-19, HIV was an independent risk factor for both severe COVID-19 at admission and in-hospital mortality. These findings have informed WHO immunisation policy that prioritises vaccination for people living with HIV. As the results mostly reflect the data contribution from Africa, this analysis will be updated as more data from other regions become available.None.For the French translation of the abstract see Supplementary Materials section.
Association Between High-Density Lipoprotein Cholesterol Levels and Adverse Cardiovascular Outcomes in High-risk Populations
Authors: Chang Liu, Devinder Dhindsa, Zakaria Almuwaqqat, Yi-An Ko, Anurag Mehta, Ayman A. Alkhoder, Zahran Alras, Shivang Rajan Desai, Krishan Jignesh Patel, Ananya Hooda, Mohamad Wehbe, Laurence S. Sperling, Yan V. Sun, Arshed A. Quyyumi
Journal: JAMA Cardiology (2022)

Previous studies have shown lower cardiovascular risk with higher high-density lipoprotein cholesterol (HDL-C) levels. However, recent data in the general population have shown increased risk of adverse outcomes at very high HDL-C concentrations.To study the association between very high HDL-C levels (>80 mg/dL) and mortality in patients with coronary artery disease (CAD) and to investigate the association of known HDL-C genotypes with high HDL-C level outcomes.This prospective, multicenter, cohort study, conducted from 2006 to present in the UK and from 2003 to present in Atlanta, Georgia, recruited patients with CAD from the UK Biobank (UKB) and the Emory Cardiovascular Biobank (EmCAB), respectively. Patients without confirmed CAD were excluded from the study. Data analyses were conducted from May 10, 2020, to April 28, 2021.High HDL-C levels (>80 mg/dL).The primary outcome was all-cause death. The secondary outcome was cardiovascular death.A total of 14 478 participants (mean [SD] age, 62.1 [5.8] years; 11 034 men [76.2%]) from the UKB and 5467 participants (mean [SD] age, 63.8 [12.3] years; 3632 men [66.4%]) from the EmCAB were included in the study. Over a median follow-up of 8.9 (IQR, 8.0-9.7) years in the UKB and 6.7 (IQR, 4.0-10.8) years in the EmCAB, a U-shaped association with outcomes was observed with higher risk in those with both low and very high HDL-C levels compared with those with midrange values. Very high HDL-C levels (>80 mg/dL) were associated with increased risk of all-cause death (hazard ratio [HR], 1.96; 95% CI, 1.42-2.71; P < .001) and cardiovascular death (HR, 1.71; 95% CI, 1.09-2.68; P = .02) compared with those with HDL-C levels in the range of 40 to 60 mg/dL in the UKB after adjustment for confounding factors. These results were replicated in the EmCAB. These associations persisted after adjustment for the HDL-C genetic risk score within the UKB. Sensitivity analyses demonstrated that the risk of all-cause mortality in the very high HDL-C group was higher among men than women in the UKB (HR, 2.63; 95% CI, 1.75-3.95; P < .001 vs HR, 1.39; 95% CI, 0.82-2.35; P = .23).Results of this cohort study suggest that very high HDL-C levels are paradoxically associated with higher mortality risk in individuals with CAD. This association was independent of the common polymorphisms associated with high HDL-C levels.
Oral Glucocorticoids for IgA Nephropathy
Authors: Kirk N. Campbell
Journal: JAMA (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Zinc oxide nanoparticles inhibit osteosarcoma metastasis by downregulating β-catenin via HIF-1α/BNIP3/LC3B-mediated mitophagy pathway
Authors: Guanping He, Jing-Jun Nie, Xiao Liu, Zihao Ding, Peng Luo, Yu Liu, Bo-Wen Zhang, Renxian Wang, Xiaoguang Liu, Yong Hai, Da-Fu Chen
Journal: Bioactive Materials (2022)

Osteosarcoma (OS) therapy faces many challenges, especially the poor survival rate once metastasis occurs. Therefore, it is crucial to explore new OS treatment strategies that can efficiently inhibit OS metastasis. Bioactive nanoparticles such as zinc oxide nanoparticles (ZnO NPs) can efficiently inhibit OS growth, however, the effect and mechanisms of them on tumor metastasis are still not clear. In this study, we firstly prepared well-dispersed ZnO NPs and proved that ZnO NPs can inhibit OS metastasis-related malignant behaviors including migration, invasion, and epithelial-mesenchymal transition (EMT). RNA-Seqs found that differentially expressed genes (DEGs) in ZnO NP-treated OS cells were enriched in wingless/integrated (Wnt) and hypoxia-inducible factor-1 (HIF-1) signaling pathway. We further proved that Zn2+ released from ZnO NPs induced downregulation of β-catenin expression via HIF-1α/BNIP3/LC3B-mediated mitophagy pathway. ZnO NPs combined with ICG-001, a β-catenin inhibitor, showed a synergistic inhibitory effect on OS lung metastasis and a longer survival time. In addition, tissue microarray (TMA) of OS patients also detected much higher β-catenin expression which indicated the role of β-catenin in OS development. In summary, our current study not only proved that ZnO NPs can inhibit OS metastasis by degrading β-catenin in HIF-1α/BNIP3/LC3B-mediated mitophagy pathway, but also provided a far-reaching potential of ZnO NPs in clinical OS treatment with metastasis.
A Perfect Pair: Stabilized Black Phosphorous Nanosheets Engineering with Antimicrobial Peptides for Robust Multidrug Resistant Bacteria Eradication (Adv. Healthcare Mater. 10/2022)
Authors: Jintao Fu, Ting Liu, Xiaoqian Feng, Yixian Zhou, Minglong Chen, Wenhao Wang, Yiting Zhao, Chao Lu, Guilan Quan, Jianfeng Cai, Xin Pan, Chuanbin Wu
Journal: Advanced Healthcare Materials (2022)
Biological aging processes underlying cognitive decline and neurodegenerative disease
Authors: Mitzi M. Gonzales, Valentina R. Garbarino, Erin Pollet, Juan P. Palavicini, Dean L. Kellogg, Ellen Kraig, Miranda E. Orr
Journal: Journal of Clinical Investigation (2022)

Alzheimer's disease and related dementias (ADRD) are among the top contributors to disability and mortality in later life. As with many chronic conditions, aging is the single most influential factor in the development of ADRD. Even among older adults who remain free of dementia throughout their lives, cognitive decline and neurodegenerative changes are appreciable with advancing age, suggesting shared pathophysiological mechanisms. In this Review, we provide an overview of changes in cognition, brain morphology, and neuropathological protein accumulation across the lifespan in humans, with complementary and mechanistic evidence from animal models. Next, we highlight selected aging processes that are differentially regulated in neurodegenerative disease, including aberrant autophagy, mitochondrial dysfunction, cellular senescence, epigenetic changes, cerebrovascular dysfunction, inflammation, and lipid dysregulation. We summarize research across clinical and translational studies to link biological aging processes to underlying ADRD pathogenesis. Targeting fundamental processes underlying biological aging may represent a yet relatively unexplored avenue to attenuate both age-related cognitive decline and ADRD. Collaboration across the fields of geroscience and neuroscience, coupled with the development of new translational animal models that more closely align with human disease processes, is necessary to advance novel therapeutic discovery in this realm.
Comprehensive Analysis of Ubiquitously Expressed Genes in Humans from a Data-Driven Perspective
Authors: Jianlei Gu, Jiawei Dai, Hui Lu, Hongyu Zhao
Journal: Genomics Proteomics & Bioinformatics (2022)

Comprehensive characterization of spatial and temporal gene expression patterns in humans is critical for uncovering the regulatory codes of the human genome and understanding the molecular mechanisms of human diseases. Ubiquitously expressed genes (UEGs) refer to the genes expressed across a majority of, if not all, phenotypic and physiological conditions of an organism. It is known that many human genes are broadly expressed across tissues. However, most previous UEG studies have only focused on providing a list of UEGs without capturing their global expression patterns, thus limiting the potential use of UEG information. In this study, we proposed a novel data-driven framework to leverage the extensive collection of ∼ 40,000 human transcriptomes to derive a list of UEGs and their corresponding global expression patterns, which offers a valuable resource to further characterize human transcriptome. Our results suggest that about half (12,234; 49.01%) of the human genes are expressed in at least 80% of human transcriptomes, and the median size of the human transcriptome is 16,342 genes (65.44%). Through gene clustering, we identified a set of UEGs, named LoVarUEGs, which have stable expression across human transcriptomes and can be used as internal reference genes for expression measurement. To further demonstrate the usefulness of this resource, we evaluated the global expression patterns for 16 previously predicted disallowed genes in islet beta cells and found that seven of these genes showed relatively more varied expression patterns, suggesting that the repression of these genes may not be unique to islet beta cells.
Dual nanoenzymes loaded hollow mesoporous organotantalum nanospheres for chemo-radio sensitization
Authors: Chao Peng, Yu Liang, Ning Su, Siwen Chen, Zhen Yuan, Yanqun Chen, Dong Wu, Bin Wu, Yang Zhang, ZiTing Xu, Si Zheng, Yingjia Li, Bingxia Zhao
Journal: Journal of Controlled Release (2022)
Clinical Trial Registration Patterns and Changes in Primary Outcomes of Randomized Clinical Trials From 2002 to 2017
Authors: Herm J. Lamberink, Christiaan H. Vinkers, Michelle Lancee, Johanna A. A. Damen, Lex M. Bouter, Willem M. Otte, Joeri K. Tijdink
Journal: JAMA Internal Medicine (2022)

This cross-sectional study evaluates the existence and timing of trial registration for randomized clinical trials (RCTs) published from 2002 to 2017 as well as substantive changes to the primary outcomes entered into registry information after those studies started.
Validity of data extraction in evidence synthesis practice of adverse events: reproducibility study
Authors: Chang Xu, Tianqi Yu, Luis Furuya-Kanamori, Lifeng Lin, Liliane Zorzela, Xiaoqin Zhou, Hanming Dai, Yoon Loke, Sunita Vohra
Journal: BMJ (2022)

Abstract Objectives To investigate the validity of data extraction in systematic reviews of adverse events, the effect of data extraction errors on the results, and to develop a classification framework for data extraction errors to support further methodological research. Design Reproducibility study. Data sources PubMed was searched for eligible systematic reviews published between 1 January 2015 and 1 January 2020. Metadata from the randomised controlled trials were extracted from the systematic reviews by four authors. The original data sources (eg, full text and ClinicalTrials.gov) were then referred to by the same authors to reproduce the data used in these meta-analyses. Eligibility criteria for selecting studies Systematic reviews were included when based on randomised controlled trials for healthcare interventions that reported safety as the exclusive outcome, with at least one pair meta-analysis that included five or more randomised controlled trials and with a 2×2 table of data for event counts and sample sizes in intervention and control arms available for each trial in the meta-analysis. Main outcome measures The primary outcome was data extraction errors summarised at three levels: study level, meta-analysis level, and systematic review level. The potential effect of such errors on the results was further investigated. Results 201 systematic reviews and 829 pairwise meta-analyses involving 10 386 randomised controlled trials were included. Data extraction could not be reproduced in 1762 (17.0%) of 10 386 trials. In 554 (66.8%) of 829 meta-analyses, at least one randomised controlled trial had data extraction errors; 171 (85.1%) of 201 systematic reviews had at least one meta-analysis with data extraction errors. The most common types of data extraction errors were numerical errors (49.2%, 867/1762) and ambiguous errors (29.9%, 526/1762), mainly caused by ambiguous definitions of the outcomes. These categories were followed by three others: zero assumption errors, misidentification, and mismatching errors. The impact of these errors were analysed on 288 meta-analyses. Data extraction errors led to 10 (3.5%) of 288 meta-analyses changing the direction of the effect and 19 (6.6%) of 288 meta-analyses changing the significance of the P value. Meta-analyses that had two or more different types of errors were more susceptible to these changes than those with only one type of error (for moderate changes, 11 (28.2%) of 39 v 26 (10.4%) 249, P=0.002; for large changes, 5 (12.8%) of 39 v 8 (3.2%) of 249, P=0.01). Conclusion Systematic reviews of adverse events potentially have serious issues in terms of the reproducibility of the data extraction, and these errors can mislead the conclusions. Implementation guidelines are urgently required to help authors of future systematic reviews improve the validity of data extraction.